Brunilda Marku

Fixed airflow obstruction due to asthma or chronic obstructive pulmonary disease: 5-year follow-up

BACKGROUND Both smokers and patients with asthma can experience fixed airflow obstruction, which is associated with distinctive patterns of airway pathology. The influence of fixed airflow obstruction on the prognosis of these patients is unknown. OBJECTIVE We sought to investigate lung function decline and exacerbations in a 5-year prospective study of subjects with fixed airflow obstruction due to asthma or chronic obstructive pulmonary disease (COPD). We also sought to explore correlations between functional, pathological, and clinical features. METHODS Patients with fixed airflow obstruction due to asthma (n = 16) or COPD (n = 21) and a control group of asthmatic patients with fully reversible airflow obstruction (n = 15) were followed for 5 years. RESULTS The rates of decline in FEV(1) were similar in patients with fixed airflow obstruction caused by asthma (-49.7 +/- 10.6 mL/y) or COPD (-51.4 +/- 9.8 mL/y) and were higher than in asthmatic patients with reversible airflow obstruction (-18.1 +/- 10.1 mL/y, P < .01). Exacerbation rates were also higher in patients with fixed airflow obstruction caused by asthma (1.41 +/- 0.26 per patient-year) or COPD (1.98 +/- 0.3 per patient-year) compared with those seen in asthmatic patients with reversible airflow obstruction (0.53 +/- 0.11 per patient-year, P < .01). Baseline exhaled nitric oxide levels and sputum eosinophil counts correlated with the FEV(1) decline in asthmatic patients with fixed airflow obstruction. By contrast, baseline sputum neutrophil counts, emphysema scores, comorbidities, and exacerbation frequency correlated directly and pulmonary diffusion capacity correlated inversely with the FEV(1) decline in patients with COPD. CONCLUSION In both patients with asthma and those with COPD, fixed airflow obstruction is associated with increased lung function decline and frequency of exacerbations. Nevertheless, the decline in lung function entails the specific pathological and clinical features of the underlying diseases.

Th2 cytokines impair innate immune responses to rhinovirus in respiratory epithelial cells

Asthma and other Th2 inflammatory conditions have been associated with increased susceptibility to viral infections. The mechanisms by which Th2 cytokines can influence immune responses to infections are largely unknown.

Long-term effects of inhaled corticosteroids on sputum bacterial and viral loads in COPD

Inhaled corticosteroid-containing medications reduce the frequency of COPD exacerbations (mainly infectious in origin) while paradoxically increasing the risk of other respiratory infections. The aim was to determine the effects of inhaled corticosteroids on airway microbial load in COPD patients and evaluate the influence of the underlying inflammatory profile on airway colonisation and microbiome. This is a proof-of-concept prospective, randomised, open-label, blinded endpoint study. Sixty patients with stable moderate COPD were randomised to receive one inhalation twice daily of either a combination of salmeterol 50 μg plus fluticasone propionate 500 μg or salmeterol 50 μg for 12 months. The primary outcome was the change of sputum bacterial loads over the course of treatment. Compared with salmeterol, 1-year treatment with salmeterol plus fluticasone was associated with a significant increase in sputum bacterial load (p=0.005), modification of sputum microbial composition and increased airway load of potentially pathogenic bacteria. The increased bacterial load was observed only in inhaled corticosteroid-treated patients with lower baseline sputum or blood eosinophil (≤2%) levels but not in patients with higher baseline eosinophils. Long-term inhaled corticosteroid treatment affects bacterial load in stable COPD. Lower eosinophil counts are associated with increased airway bacterial load. Long term inhaled corticosteroids increase airway bacterial load in COPD patients with low eosinophil counts http://ow.ly/8nO530eMSza

Regular versus as-needed budesonide and formoterol combination treatment for moderate asthma: a non-inferiority, randomised, double-blind clinical trial

BACKGROUND Treatment guidelines for patients with moderate persistent asthma recommend regular therapy with a combination of an inhaled corticosteroid and a longacting β2 agonist plus as-needed rapid-acting bronchodilators. We investigated whether symptom-driven budesonide and formoterol combination therapy administered as needed would be as effective as regular treatment with this combination plus as-needed symptom-driven terbutaline for patients with moderate asthma. METHODS In this non-inferiority randomised clinical trial, we recruited adult patients (18-65 years of age) with stable moderate persistent asthma, according to 2006 Global Initiative for Asthma guidelines. Patients were recruited from outpatient clinics of secondary and tertiary referral hospitals and university centres. After a 6-week run-in period of inhaled regular budesonide and formoterol plus as-needed terbutaline, the patients were randomly assigned in a 1:1 ratio to receive placebo twice daily plus as-needed treatment with inhaled 160 μg budesonide and 4·5 μg formoterol (as-needed budesonide and formoterol therapy) or twice-daily 160 μg budesonide and 4·5 μg formoterol combination plus symptom-driven 500 μg terbutaline (regular budesonide/formoterol therapy) for 1 year. Randomisation was done according to a list prepared with the use of a random number generator and a balanced-block design stratified by centre. Patients and investigators were masked to treatment assignment. The primary outcome was time to first treatment failure measured after 1 year of treatment using Kaplan-Meier estimates, and the power of the study was calculated based on the rate of treatment failure. Analyses were done on the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT00849095. FINDINGS Between April 20, 2009, and March 31, 2012, we screened 1010 patients with moderate asthma and randomly assigned 866 eligible patients to the two treatment groups (424 to as-needed budesonide and formoterol therapy and 442 to regular budenoside and formoterol therapy). Compared with regular budesonide and formoterol therapy, as-needed budesonide and formoterol treatment was associated with a lower probability of patients having no treatment failure at 1 year (Kaplan-Meier estimates 53·6% for as-needed treatment vs 64·0% for regular treatment; difference 10·3% [95% CI 3·2-17·4], at a predefined non-inferiority limit of 9%). Patients in the as-needed budesonide and formoterol group had shorter time to first treatment failure than those in the regular therapy group (11·86 weeks vs 28·00 weeks for the first quartile [ie, the time until the first 25% of patients experienced treatment failure]). The difference in treatment failures was largely attributable to nocturnal awakenings (82 patients in the as-needed treatment group vs 44 in the regular treatment group). Both treatment regimens were well tolerated. INTERPRETATION In patients with moderate stable asthma, as-needed budesonide and formoterol therapy is less effective than is the guideline-recommended regular budesonide and formoterol treatment, even though the differences are small. FUNDING Italian Medicines Agency.

Assessing small airway impairment in mild-to-moderate smoking asthmatic patients

Asthma is characterised by airway inflammation throughout the bronchial tree, including the small airways. In asthma, small airway alterations are associated with poor clinical outcomes [1]. Cigarette smoke is known to induce peripheral airway abnormalities, asthmatic smokers exhibit a more rapid lung function decline, experience more frequent exacerbations and are more likely to be uncontrolled, even when the disease is managed as recommended [2]. The mechanisms accounting for poor responses to treatment in smoking asthmatic patients are currently unclear, although low accessibility to inhaled medications in the peripheral airways is considered a limiting factor for the efficacy of such treatments [3]. Cigarette smoking enhances small airways impairment in asthmatic patients http://ow.ly/WWUky

Reducing agents decrease the oxidative burst and improve clinical outcomes in COPD patients: a randomised controlled trial on the effects of sulphurous thermal water inhalation.

Background. Inhalation of thermal water with antioxidant properties is empirically used for COPD. Aims. To evaluate the effects of sulphurous thermal water (reducing agents) on airway oxidant stress and clinical outcomes in COPD. Methods. Forty moderate-to-severe COPD patients were randomly assigned to receive 12-day inhalation with sulphurous thermal water or isotonic saline. Patients were assessed for superoxide anion (O2 −) production in the exhaled breath condensate and clinical outcomes at recruitment, the day after the conclusion of the 12-day inhalation treatment, and one month after the end of the inhalation treatment. Results. Inhalation of reducing agents resulted in a significant reduction of O2 − production in exhaled breath condensate of COPD patients at the end of the inhalatory treatment and at followup compared to baseline. A significant improvement in the COPD assessment test (CAT) questionnaire was shown one month after the end of the inhalatory treatment only in patients receiving sulphurous water. Conclusion. Thermal water inhalation produced an in vivo antioxidant effect and improvement in health status in COPD patients. Larger studies are required in order to evaluate whether inhalation of thermal water is able to modify relevant clinical outcomes of the disease (the study was registered at clinicaltrial.gov—identifier: NCT01664767).